tbuckley/cabot-search huggingface dataset:
Abstract 6337: Assessing genomic literacy among medical trainees and practitioners in Pakistan
Authors: Madina Barakzai, Shagufta Rehmat, Faisal F. Khan
Journal: Cancer Research (2022)

Abstract Genomic literacy has a significant impact on the successful application and deployment of new practices such as precision medicine. It can be described as the ability to achieve, process, understand, and apply genomic knowledge to health-related decision-making. The aim of this study is to assess the level of genomic literacy, including the knowledge of genetic testing, its outcomes, and its significance among medical trainees and practitioners in Pakistan. This study also offers recommendations for improving genomic literacy within the medical community in Pakistan. A cross-sectional study for which an online questionnaire was designed in the English language using Google Forms. The questionnaire was distributed among trainees and practitioners across Pakistan through online social media platforms. The survey comprised of 36 questions categorized into three sections namely demographics, quantitative questions, and knowledge section. A total of 219 medical professionals (56% trained in medicine while 44% in Dentistry) responded to the survey. Medical practitioners from 27 different cities across Pakistan participated in the survey but with a clear bias towards the city of Peshawar (90%). The majority of the participants (57.5%) were trainee medical officers. Most of the participants in this cohort were aware of genetics, the genome, and PCR technology but 74.9% were not familiar with genetic tests in their specialty. The mean total score for the multiple-choice questions among the participants was 62.5% graduates of medicine (65%) outperforming those in dentistry (59%). Participants were asked about their interest in further learning opportunities about genomics, for which 71% answered in affirmation, however, the remaining were not overly interested. Genomic literacy level can be considered satisfactory at the level of classical genetics, yet there is a clear need for training in molecular biology concepts such as protein synthesis, gene expression, and genome structure within the medical community. With a limited sample size and diversity of respondents, the subject warrants a broader survey to assess genomic literacy which can help in better planning for wider adoption of genomic testing in the medical community. Findings of this survey also highlight the need for assessing medical communities in other low-resource and underprivileged settings to help enhance our understanding and avoid a looming ‘genomics divide’. Citation Format: Madina Barakzai, Shagufta Rehmat, Faisal F. Khan. Assessing genomic literacy among medical trainees and practitioners in Pakistan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6337.
Delays in melanoma presentation during the COVID-19 pandemic: A nationwide multi-institutional cohort study
Authors: Nicole Trepanowski, Michael S. Chang, Guohai Zhou, Maham Ahmad, Elizabeth G. Berry, Katherine Bui, William H. Butler, Emily Y. Chu, Clara Curiel-Lewandrowski, Laura E. Dellalana, Darrel L. Ellis, S. Caleb Freeman, Pavane L. Gorrepati, Douglas Grossman, Samvel Gyurdzhyan, Peter A. Kanetsky, Amber Loren Ong King, Avani M. Kolla, Christine G. Lian, Jennifer Y. Lin, Vincent Liu, Annie Lowenthal, Kelly N. McCoy, Ananya Munjal, Caitlyn N. Myrdal, Sara Perkins, Jennifer G. Powers, Corinne Rauck, Tristan C. Smart, Jennifer A. Stein, Suraj Venna, Madalyn E. Walsh, Jennifer Y. Wang, Sancy A. Leachman, Susan M. Swetter, Rebecca I. Hartman
Journal: Journal of the American Academy of Dermatology (2022)
Drivers of adaptive evolution during chronic SARS-CoV-2 infections
Authors: Sheri Harari, Maayan Tahor, Natalie Rutsinsky, Suzy Meijer, Danielle Miller, Oryan Henig, Ora Halutz, Katia Levytskyi, Ronen Ben-Ami, Amos Adler, Yael Paran, Adi Stern
Journal: Nature Medicine (2022)

Abstract In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient’s body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence.
Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial
Authors: Noemie Jourde-Chiche, Nathalie Costedoat-Chalumeau, Karine Baumstarck, Anderson Loundou, Laurence Bouillet, Stéphane Burtey, Valérie Caudwell, Laurent Chiche, Lionel Couzi, Laurent Daniel, Christophe Deligny, Bertrand Dussol, Stanislas Faguer, Pierre Gobert, Guillaume Gondran, Antoine Huart, Aurélie Hummel, Emilie Kalbacher, Adexandre Karras, Marc Lambert, Véronique Le Guern, Ludivine Lebourg, Sandrine Loubière, Hélène Maillard-Lefebvre, François Maurier, Micheline Pha, Viviane Queyrel, Philippe Remy, Françoise Sarrot-Reynauld, David Verhelst, Eric Hachulla, Zahir Amoura, Eric Daugas
Journal: Annals of the Rheumatic Diseases (2022)

Objectives Lupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with induction immunosuppressive therapy (IST), followed by maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST is unknown. The WIN-Lupus trial tested whether IST discontinuation after 2‒3 years was non-inferior to IST continuation for two more years in proliferative LN. Methods WIN-Lupus was an investigator-initiated multicentre randomised controlled trial. Patients receiving maintenance IST with azathioprine or mycophenolate mofetil for 2–3 years, and hydroxychloroquine, were randomised (1:1) into two groups: (1) IST continuation and (2) IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Main secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events. Results Between 2011 and 2016, 96 patients (out of 200 planned) were randomised in WIN-Lupus: IST continuation group (n=48), IST discontinuation group (n=48). Relapse of proliferative LN occurred in 5/40 (12.5%) patients with IST continuation and in 12/44 (27.3%) patients with IST discontinuation (difference 14.8% (95% CI −1.9 to 31.5)). Non-inferiority was not demonstrated for relapse rate; time to relapse did not differ between the groups. Severe SLE flares (renal or extrarenal) were less frequent in patients with IST continuation (5/40 vs 14/44 patients; p=0.035). Adverse events did not differ between the groups. Conclusions Non-inferiority of maintenance IST discontinuation after 2‒3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flares. Trial registration number NCT01284725 .
Epicardial HDAC3 Promotes Myocardial Growth Through a Novel MicroRNA Pathway
Authors: Jihyun Jang, Guang Song, Sarah M. Pettit, Qinshan Li, Xiaosu Song, Chen-leng Cai, Sunjay Kaushal, Deqiang Li
Journal: Circulation Research (2022)

Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells instruct myocardial growth by secreting essential factors including FGF (fibroblast growth factor) 9 and IGF (insulin-like growth factor) 2. However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation. The current study is to investigate whether and how HDAC (histone deacetylase) 3 in the developing epicardium regulates myocardial growth. Various cellular and mouse models in conjunction with biochemical and molecular tools were employed to study the role of HDAC3 in the developing epicardium. We deleted Hdac3 in the developing murine epicardium, and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of epicardium-derived cells. The cultured embryonic cardiomyocytes with supernatants from Hdac3 knockout (KO) mouse epicardial cells also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that Fgf9 and Igf2 were significantly downregulated in Hdac3 KO mouse epicardial cells. We further found that Fgf9 and Igf2 expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by Hdac3 KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in Hdac3 KO mouse epicardial cells and Hdac3 epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in Hdac3 KO mouse epicardial cells. Our findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322 or miR-503, providing novel insights in elucidating the etiology of congenital heart defects and conceptual strategies to promote myocardial regeneration.
Abstract 6336: Regulation of tissue factor dependent procoagulant properties by CD44: Implication for metastasis of breast tumor cells
Authors: Amélie V. Villard, Anthony Genna, Christine Gilles
Journal: Cancer Research (2022)

Abstract The aim here is to study the implication of the stem cell marker and fibrin receptor, CD44, in the regulation of tissue factor and its associated pro-coagulant and pro-metastatic properties in breast tumor cells. We examined this CD44/TF/coagulation axis in breast cancer EMT+ (MDA-MB-231, Hs578T), EMT- (MCF7, T47D) and EMT-inducible (EGF-treated MDA-MB-468, MDA-MB-468 harboring a doxycycline-inducible snail expression vector) cellular models. We used siRNA to inhibit CD44 expression and realized RT-qPCR, western blot, flow cytometry analyzes and promoter reporter assays to monitor regulations of our gene of interest. Furthermore, we realized in vitro clotting assays and TF activity assays to examine coagulant properties, and in vivo experimental metastasis assays to assess early metastatic potential. We first confirmed by WB, RT-qPCR and FACS analyzes that CD44 is over-expressed in our EMT+ and EMT-induced (EMTi) cellular models, concomitantly with TF expression. Using siRNAs, we showed that CD44 silencing in these same EMT+ and EMTi cellular models decreased both mRNA and protein levels of TF. Clotting assays and TF activity assays further showed that CD44 silencing decreased pro-coagulant properties of our EMT+ and EMTi cellular models in vitro and of their pro-metastatic properties in vivo. Examining further the molecular mechanisms of TF regulation by CD44, we employed truncated TF promoter reporter vectors to identify key transcription factors linking CD44 to TF transcription. These experiments revealed that a TF promoter region containing Sp1 binding sites is sufficient to mediate the diminution of TF promoter activity seen after CD44 silencing. Mutations in the Sp1 binding sites abrogated the activity of the TF reporter vector. Further pointing to Sp1 as a key transcription factor implicated in TF regulation by CD44, we observed that silencing CD44 inhibited Sp1 expression and that silencing Sp1 decreased TF mRNA levels. Our results thus demonstrate a key role of CD44 in regulating TF expression in EMT+ cancer cells, and point to Sp1 as a transcriptional mediator of this regulation. This modulation of TF expression by CD44 in EMT+ cells led to a concomitant regulation of pro-coagulant properties, and impacts metastatic potential. Citation Format: Amélie V. Villard, Anthony Genna, Christine Gilles. Regulation of tissue factor dependent procoagulant properties by CD44: Implication for metastasis of breast tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6336.
SIRPα Mediates IGF1 Receptor in Cardiomyopathy Induced by Chronic Kidney Disease
Authors: Sandhya S. Thomas, Jiao Wu, Giovanni Davogustto, Michael W. Holliday, Kristin Eckel-Mahan, Daniela Verzola, Giacomo Garibotto, Zhaoyong Hu, William E. Mitch, Heinrich Taegtmeyer
Journal: Circulation Research (2022)

Chronic kidney disease (CKD) is characterized by increased myocardial mass despite near-normal blood pressure, suggesting the presence of a separate trigger. A potential driver is SIRPα (signal regulatory protein alpha)-a mediator impairing insulin signaling. The objective of this study is to assess the role of circulating SIRPα in CKD-induced adverse cardiac remodeling.
Identification of early neurodegenerative pathways in progressive multiple sclerosis
Authors: Max Kaufmann, Anna-Lena Schaupp, Rosa Sun, Fabian Coscia, Calliope A. Dendrou, Adrian Cortes, Gurman Kaur, Hayley G. Evans, Annelie Mollbrink, José Fernández Navarro, Jana K. Sonner, Christina Mayer, Gabriele C. DeLuca, Joakim Lundeberg, Paul M. Matthews, Kathrine E. Attfield, Manuel A. Friese, Matthias Mann, Lars Fugger
Journal: Nature Neuroscience (2022)
The Case | Inflammatory polyarthritis in a kidney transplant recipient
Authors: Karthikeyan Manoharan, Priyansh Gupta, Hitaishi Mehta, Ritambhra Nada, Aravind Sekar, Ashwani Kumar, Aman Sharma, Manish Rathi, Harbir Singh Kohli, Keshavamurthy Vinay, Raja Ramachandran
Journal: Kidney International (2022)
Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
Authors: Douglas P. Wightman, Iris E. Jansen, Jeanne E. Savage, Alexey A. Shadrin, Shahram Bahrami, Dominic Holland, Arvid Rongve, Sigrid Børte, Bendik S. Winsvold, Ole Kristian Drange, Amy E. Martinsen, Anne Heidi Skogholt, Cristen Willer, Geir Bråthen, Ingunn Bosnes, Jonas Bille Nielsen, Lars G. Fritsche, Laurent F. Thomas, Linda M. Pedersen, Maiken E. Gabrielsen, Marianne Bakke Johnsen, Tore Wergeland Meisingset, Wei Zhou, Petroula Proitsi, Angela Hodges, Richard Dobson, Latha Velayudhan, Karl Heilbron, Adam Auton, Michelle Agee, Stella Aslibekyan, Elizabeth Babalola, Robert K. Bell, Jessica Bielenberg, Katarzyna Bryc, Emily Bullis, Briana Cameron, Daniella Coker, Gabriel Cuellar Partida, Devika Dhamija, Sayantan Das, Sarah L. Elson, Teresa Filshtein, Kipper Fletez-Brant, Pierre Fontanillas, Will Freyman, Pooja M. Gandhi, Barry Hicks, David A. Hinds, Karen E. Huber, Ethan M. Jewett, Yunxuan Jiang, Aaron Kleinman, Katelyn Kukar, Vanessa Lane, Keng-Han Lin, Maya Lowe, Marie K. Luff, Jey C. McCreight, Matthew H. McIntyre, Kimberly F. McManus, Steven J. Micheletti, Meghan E. Moreno, Joanna L. Mountain, Sahar V. Mozaffari, Priyanka Nandakumar, Elizabeth S. Noblin, Jared O’Connell, Aaron A. Petrakovitz, G. David Poznik, Morgan Schumacher, Anjali J. Shastri, Janie F. Shelton, Jingchunzi Shi, Suyash Shringarpure, Chao Tian, Vinh Tran, Joyce Y. Tung, Xin Wang, Wei Wang, Catherine H. Weldon, Peter Wilton, Julia M. Sealock, Lea K. Davis, Nancy L. Pedersen, Chandra A. Reynolds, Ida K. Karlsson, Sigurdur Magnusson, Hreinn Stefansson, Steinunn Thordardottir, Palmi V. Jonsson, Jon Snaedal, Anna Zettergren, Ingmar Skoog, Silke Kern, Margda Waern, Henrik Zetterberg, Kaj Blennow, Eystein Stordal, Kristian Hveem, John-Anker Zwart, Lavinia Athanasiu, Per Selnes, Ingvild Saltvedt, Sigrid B. Sando, Ingun Ulstein, Srdjan Djurovic, Tormod Fladby, Dag Aarsland, Geir Selbæk, Stephan Ripke, Kari Stefansson, Ole A. Andreassen, Danielle Posthuma
Journal: Nature Genetics (2022)
Emergence and widespread circulation of a recombinant SARS-CoV-2 lineage in North America
Authors: Bernardo Gutierrez, Hugo G. Castelán Sánchez, Darlan da Silva Candido, Ben Jackson, Shay Fleishon, Renaud Houzet, Christopher Ruis, Luis Delaye, Nuno R. Faria, Andrew Rambaut, Oliver G. Pybus, Marina Escalera-Zamudio
Journal: Cell Host & Microbe (2022)

Although recombination is a feature of coronavirus evolution, previously detected recombinant lineages of SARS-CoV-2 have shown limited circulation thus far. Here, we present a detailed phylogenetic analysis of four SARS-CoV-2 lineages to investigate the possibility of virus recombination among them. Our analyses reveal well-supported phylogenetic differences between the Orf1ab region encoding viral non-structural proteins and the rest of the genome, including Spike (S) protein and remaining reading frames. By accounting for several deletions in NSP6, Orf3a, and S, we conclude that the B.1.628 major cluster, now designated as lineage XB, originated from a recombination event between viruses of B.1.631 and B.1.634 lineages. This scenario is supported by the spatiotemporal distribution of these lineages across the USA and Mexico during 2021, suggesting that the recombination event originated in this geographical region. This event raises important questions regarding the role and potential effects of recombination on SARS-CoV-2 evolution.
Kalium channelrhodopsins are natural light-gated potassium channels that mediate optogenetic inhibition
Authors: Elena G. Govorunova, Yueyang Gou, Oleg A. Sineshchekov, Hai Li, Xiaoyu Lu, Yumei Wang, Leonid S. Brown, François St-Pierre, Mingshan Xue, John L. Spudich
Journal: Nature Neuroscience (2022)
Abstract 6341: ImaGene: A robust AI-based software platform for tumor radiogenomic evaluation and reporting
Authors: Shrey S. Sukhadia, Aayush Tyagi, Vivek Venkatraman, Pritam Mukherjee, Prathosh A.P., Mayur Divate, Olivier Gevaert, Shivashankar H. Nagaraj
Journal: Cancer Research (2022)

Abstract The field of radiomics has undergone several advancements in approaches to uncovering hidden quantitative features from tumor imaging data for use in guiding clinical decision-making for cancer patients. Radiographic imaging techniques provide insight into the imaging features of tumor regions of interest (ROIs), while immunohistochemistry and sequencing techniques performed on biopsy samples yield omics data. These imaging and omics feature data can then be correlated and modeled using artificial intelligence (AI) techniques to highlight notable associations between tumor genotype and phenotype. Currently, however, the radiogenomics field lacks a unified and robust software platform capable of algorithmically analyzing imaging and omics features using modifiable parameters, detecting significant relationships among these features, and subjecting them to AI-based analysis. To address this gap, we developed ImaGene, a robust AI-based platform that uses omics and imaging features as inputs for different tumor types, performs statistical analyses of the correlations between these data types, and constructs AI models based upon significantly correlated features. It has several modifiable configuration parameters that provide users with complete control over their experiments. For each run, ImaGene produces comprehensive reports that can contribute to the construction of a novel radiogenomic knowledge base, in addition to enabling the deployment and sharing of AI models. To demonstrate the utility of ImaGene, we acquired imaging and omics datasets pertaining to Invasive Breast Cancer (IBC) and Head and Neck Squamous Cell Carcinoma (HNSCC) from public databases and analyzed them with this platform using specific parameters. In both cases, we uncovered significant associations between several imaging features and 11 genes: CRABP1, VRTN, SMTNL2, FABP1, HAND2, HAS1, C4BPA, FAM163A, DSG1, SMTNL2 and KCNJ16 for IBC, and 10 genes: CEACAM6, IGLL1, SERPINA1, NANOG, OCA2, PRLR, ACSM2B, CYP11B1, and VPREB1 for HNSCC. Overall, our software platform is capable of identifying, analyzing, and correlating important features from tumor scans, thereby providing researchers with a reliable and accurate tool for their radiogenomics experiments. We anticipate that ImaGene will become the gold standard for tumor analyses in the field of radiogenomics owing to its ease of use, flexibility, and reproducibility. Citation Format: Shrey S. Sukhadia, Aayush Tyagi, Vivek Venkatraman, Pritam Mukherjee, Prathosh A.P., Mayur Divate, Olivier Gevaert, Shivashankar H. Nagaraj. ImaGene: A robust AI-based software platform for tumor radiogenomic evaluation and reporting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6341.
Correction to: Management of moderate to severe traumatic brain injury: an update for the intensivist
Authors: Geert Meyfroidt, Pierre Bouzat, Michael P. Casaer, Randall Chesnut, Sophie Rym Hamada, Raimund Helbok, Peter Hutchinson, Andrew I. R. Maas, Geoffrey Manley, David K. Menon, Virginia F. J. Newcombe, Mauro Oddo, Chiara Robba, Lori Shutter, Martin Smith, Ewout W. Steyerberg, Nino Stocchetti, Fabio Silvio Taccone, Lindsay Wilson, Elisa R. Zanier, Giuseppe Citerio
Journal: Intensive Care Medicine (2022)